The most frequently studied stimulants of angiogenesis in bladder cancer are VEGF, thymidine phosphorylase, matrix metalloproteinases (basic fibroblast growth factor b-FGF), carbonic anhydrase 9, and cyclo-oxygenase 2, while the most studied suppressors include angiostatin
, endostatin, p53 and thrombospondin-1 (11).
This complex process is controlled via an appropriate balance between angiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (1) and antiangiogenic factors such as thrombospondin-1, endostatin, and angiostatin
. (2) Angiogenesis is a necessary step in several physiological conditions, including embryogenesis, (3,4) wound healing, (5) and reconstruction of the uterine endometrium the during menstrual cycle.
Among these factors it can be pointed to angiostatin
, endostatin, vasostatin, certain interleukins (ILs) such as IL-4 and IL-12 and also alpha, beta, and gamma interferons (IFNs).
Bloom et al., "Endothelial progenitor cells as putative targets for angiostatin
," Cancer Research, vol.
Mraovic et al., "Chronic hyperglycemia attenuates coronary collateral development and impairs proliferative properties of myocardial interstitial fluid by production of angiostatin
," Circulation, vol.
Several other molecules also play an antiangiogenic role, including endostatin, angiostatin
, and tissue inhibitors of metalloproteinases (TIMPs).
Tumor necrosis factor-alpha and angiostatin
are mediators of endothelial cytotoxicity in bronchoalveolar lavages of patients with acute respiratory distress syndrome.
On the other hand, angiostatin
, endostatin, and thrombospondin inhibit angiogenesis [7-9].
Carrozzino et al., "Neutrophils as a key cellular target for angiostatin
: implications for regulation of angiogenesis and inflammation," FASEB Journal, vol.
, derived from plasminogen, able to suppress proliferation and migration, induces endothelial cells apoptosis [84, 85] and additionally downregulates VEGF expression [86-88].
Primer sequences used were the following: [beta]-actin, forward 5-CCT CTA TGC CAA CAC AGT 3' and reverse 5-AGC CAC CAA TCC ACA CAG 3; CYLD, forward 5-AAT GTG TCC CTG CCC TAC CTA 3' and reverse 5-CTC GTC CCT ACT CTG CCA CTT 3'; PEDF, forward 5-GAG GAC AGG ACC GTG AGA GT 3' and reverse 5'-GGG CAG GAA GAA GAT GAT G 3;VEGF, forward 5-GCA AGA GAA GAC ACG GTG GT 3' and reverse 5'-CAG GAG GTG GGG TAA GGA G 3; PDGF, forward 5-CAG TGT CCG TTT GTT CAG TG 3' and reverse 5'-TGG TTT TGT TTT CGC TCT CT 3; and angiostatin
, forward 5-CCT TGG TGC TAC ACT ACA GA 3 and reverse 5'-GGA GAT TTT GCC CTC ATA C 3'.
Tumors may activate angiogenic inhibitors (angiostatin
and endostatin) that can modulate angiogenesis at both the primary site and downstream sites of metastasis [3, 4], when a tumor successfully spreads to other parts of the body using the blood or lymph systems known as metastasis.